The invention relates to a time-of-flight mass spectrometer for injection of the ions orthogonally to the time-resolving axis-of-flight component, with a pulser for acceleration of the ions of the beam in the axis-of-flight direction, preferredly with a velocity-focusing reflector for reflecting the ion beam and with a flat detector at the end of the flight section.
The invention consists of using, both for acceleration in the pulser and for reflection in the reflectors, a gridless optical system made up of slit diaphragms which can spatially focus the ions onto the detector in the direction vertical to the directions of injection and flight axis, but which does not have any focusing or deflecting effect on the other directions. For some reflector geometries it is essential to use an additional cylindrical lens for focusing, and for other reflector geometries the use of such a lens may be advantageous.
Time-of-flight mass spectrometers, which have been known for over 50 years now, have seen a dramatic comeback over roughly the last ten years. On the one hand, these devices can be used advantageously for new types of ionization with which large biomolecules can be ionized, and on the other hand the development of fast electronics for digitizing the temporally fast-changing ion beam in the detector has made it possible to construct high-resolution apparatuses. Nowadays analog/digital converters with a dynamic range of 8 bits and a data conversion rate of up to 4 gigahertz are available, and for measuring individual ions there are time/digital converters available with temporal resolutions in the picosecond range.
Time-of-flight mass spectrometers are frequently abbreviated to TOF or TOF-MS (xe2x80x9cTime-Of-Flight Mass Spectrometerxe2x80x9d).
Two different types of time-of-flight mass spectrometer have been developed. The first type comprises time-of-flight mass spectrometers for measuring ions generated as ion cloud pulses in flight direction. An example for this is the generation of ions by matrix-assisted laser de-sorption, abbreviated to MALDI, a method of ionization suitable for ionizing large molecules. The second type consists of mass spectrometers for continuous injection of an ion beam, from which a section is then outpulsed in a xe2x80x9cpulserxe2x80x9d at right angles to the direction of injection and is caused to fly through the mass spectrometer in the form of a band-shaped ion beam consisting of linear ion beam segments. This second type is abbreviated to xe2x80x9cOrthogonal Time-Of-Flight Mass Spectrometerxe2x80x9d (OTOF); it is chiefly used in conjunction with continuous ion generation, for example electrospray (ESI). Due to the very high number of pulsed processes per unit of time (up to 50,000 pulses per second) a high number of spectra, each with a low number of ions, is generated in order to exploit the ions of the continuous beam as efficiently as possible. Electrospray is also suitable for the ionization of large molecules.
For measurement of the mass of large molecules by mass spectrometry, as particularly occurs in biochemistry, there is no spectrometer which is better than a time-of-flight mass spectrometer because of the limited mass ranges of other mass spectrometers.
Pulsed ion beams with ion cloud pulses originating from small sample spots, on the one hand, and band-shaped ion beams on the other, call for different ion optical systems for further focusing and guidance through the time-of-flight mass spectrometer: this is the reason for developing different types of mass spectrometer for these different types of ion injection.
In the simplest case of a TOF mass spectrometer, the ions are not focused at all. Acceleration of the ions generated by MALDI or ESI is performed by one or two grids, and the slight divergence of the ion beam caused by the initial velocities of the ions perpendicular to the direction of acceleration is accepted as being tolerable. The reflector also contains grids, one or even two grids depending on the type of reflector. In addition to beam divergence due to the spread of initial velocities there is a beam divergence caused by the small-angle scatter at the openings of the grid. If the electric field strength Is different on both sides of the grid, each opening in the grid will act as a weak ion lens. Divergence due to the spread of initial velocities can be reduced by selecting a high acceleration voltage but the small-angle scatter at the openings in the grid cannot be reduced. This small-angle scatter can only be reduced by making nets of finer mesh, albeit at the expense of grid transparency. Beam divergence creates a larger beam cross-section at the location of the detector, which necessitates a large-area detector. This large-area detector has disadvantages: a high level of noise and the necessity of very good two-dimensional directional adjustment in order to keep the flight path differences well below one micrometer.
For an optical system with two acceleration grids and one two-stage reflector with two grids, which each have to be transversed twice, there are already six grid passages. Even if the grids have a high level of transparency at 90%, which can only be achieved if the thickness of the grid wires is only about 5% of mesh size, total transparency is still only 48%. In addition there will be a non-negligible number of ions which are reflected by the grids and can be scattered back to the detector where they create background noise, which worsens signal-to-noise ratio.
The use of grids has therefore generally led to the use of single-stage reflectors. These must be much longer, about ⅓ of the total length of the spectrometer. The advantages of having only one grid (only two ion passages instead of four) and having to generate only one adjustable voltage are offset by considerable drawbacks: The mechanical design calls for many more diaphragms for homogenization of the reflection field; the long stay of the ions in the reflection field, however, leads to an increase in metastable decompositions in the reflector and therefore to diffused background noise in the spectrum because the decomposing ions turn back somewhere in the reflector due to changed energies so they cannot be temporally focused.
For the case of point-shaped ion origins (MALDI for example) gridless optical systems were therefore developed and introduced for acceleration of the ions (U.S. Pat. No. 5,742,049), particularly for their reflection in a two-stage reflector (EP 0 208 894). The gridless optical system consists of circular apertures which in principle represent spherical lenses. The ions from the point-shaped ion origin are therefore also imaged on a small-area detector (almost) in the shape of a point.
All the mass spectrometers known for orthogonal injection, however, have the very disadvantageous grids (due to the band-shaped ion beam which does not permit spherical lenses), both in the pulser and in the reflector.
It is the objective of the invention to find an accelerating and reflecting optical system for a time-of-flight mass spectrometer with orthogonal injection which operates without disadvantageous grids and focuses the ions on a small-area detector.
Throughout this text, we shall use the following nomenclature:
1) the original flight direction of the orthogonally injected ions defines the x-direction,
2) the direction in which the ions are pulsed by the pulser defines the y-direction,
3) the z-direction is defined to be perpendicular to the x- and y-direction. The three directions are orthogonal to each other; the y-direction is not completely identical with the flight path of the ions after being pulsed by the pulser.
The invention consists of using grid-free optical slit devices with long slits in the x-direction for the acceleration or deceleration of the in x-direction extended ion beam segments, both in the pulser and in the reflector (or in the reflectors if more than one is used), the optical slit devices being able to focus the band-shaped ion beam segments in the z-direction on a detector, which is narrow in the z-direction but long in the x-direction, if necessary with an additional cylindrical lens.
The slit diaphragms of the pulser, which accelerates the ions in the y-direction, act as slightly divergent cylindrical lenses in the z-direction so they create an ion beam which diverges slightly in the z-direction. If a Mamyrin two-stage reflector is used with a first strong deceleration field and a second weaker reflection field, the two being separated from the drift section and separated from one another by a grid-free passage gap extended in the x-direction, the reflector forms a (reflecting) cylindrical convergent lens in the z-direction, the focal length of which is determined by the slit widths and the ratio between deceleration field strength and reflection field strength. In the z-direction this cylindrical convergent lens can focus the slightly in the z-direction diverging ion beam from the pulser on the detector even without any additional cylindrical lens.
It is quite advantageous to use a two-stage Mamyrin reflector with a short deceleration field although it requires two supply voltages. The separation of deceleration field and reflector field permits an electrical adjustment of the velocity focusing exactly for the location of the detector; this makes mass resolution easier to adjust electrically without shortening the effective length of the flight. The crucial reduction in background noise has already been mentioned above.
For a single-stage reflector with only one slit diaphragm between the drift section and the reflection field at least one cylindrical lens must be added to be able to focus the ion beam on the detector in the z-direction because the single-stage reflector with slit diaphragms in the z-direction represents a cylindrical divergent lens.
Since the z-divergence of the ion beam leaving the pulser necessitates very wide slit diaphragms at the two-stage reflector, it is useful to install a cylindrical lens between the pulser and the reflector, making the ion beam narrower in the z-direction. The cylindrical lens can be a cylindrical Einzel lens. It is particularly advantageous to place the cylindrical lens close to the pulser and set it electrically so that an initial focusing in the z-direction is achieved between the pulser and the reflector. A focus line is formed, expanded linearly in the x-direction (almost perpendicular to the direction of flight) and located between the pulser and the reflector. This focus line is then focused, in the z-direction, onto the detector by the two-stage reflector. Another reason why installation of the cylindrical lens is particularly advantageous is that the ratio between deceleration field strength and reflection field strength in the reflector not only sets spatial z-focal length but also velocity focusing (and hence temporal focusing) at the detector, which takes absolute priority in achieving a high temporal resolution (and therefore mass resolving power). The cylindrical lens thus makes it possible to set the focusing length of the entire arrangement in the z-direction irrespective of velocity focusing.
A cylindrical Einzel lens consists of three slit diaphragms, the two outer ones of which are at the same potential, that is, the potential of the surroundings, and the inner slit diaphragm is at an adjustable lens potential, which determines the focal length of the lens. By making the potentials slightly different at the two jaws of the center slit diaphragm, the cylindrical Einzel lens can also be used to adjust the ion beam in the z-direction, in order to direct the band-shaped ion beam exactly into the center plane of the reflector.
It is advantageous to use a pulser with two slits and therefore two acceleration fields. That makes it possible to keep the voltage low at the first acceleration field which has to be pulsed: the voltage to be switched is only a small fraction of the total acceleration voltage. Pulsing has to take place at a rise time of a few nanoseconds and a low voltage facilitates the task of electronically developing such a pulser. A two-stage pulser can also bring about spatial or velocity focusing of the ions from the pulser.
The pulser and detector do not have to be positioned in the same x-z plane. Due to the electrical adjustability of the focal lengths of the cylindrical Einzel lens and the reflector, the detector can be positioned in a different x-z plane in front of or behind the pulser.
Finally the band-shaped ion beam segment can also be reflected a number of times in a zig-zag shape by more than one reflector with slit lenses before it hits the detector. The zig-zag deflection can take place in the x-y plane (FIG. 3) but also by slightly tilting the reflector round the longitudinal axis of the entrance slits in the x-z plane (FIG. 2). The latter can favorably be performed using a deflection capacitor, preferably an xe2x80x9cextended Bradbury-Nielsen gatexe2x80x9d in accordance with U.S. Pat. No. 5,986,258, which brings the direction of ion flight into the y-direction. By applying this deflection capacitor to deflect the beam into the y-direction the detector can then be positioned under or above the pulser.